Community-acquired pneumonia and influenza are the 8th most frequent primary and important secondary causes of death in the US. An accurate determination of the population-based incidence is critical to determine the opportunities for prevention, such as expansion of serotypes included in the conjugate pneumococcal vaccine and possible use in adults. A large body of information suggests that the etiology and possibly the frequency of CAP have changed since the last CDC-sponsored population-based study. Even the definition of which patients are included as community-acquired pneumonia has undergone revision, unfortunately without an appropriate population-based analysis of the pathogen-specific incidence. Developments in molecular diagnostic techniques, such as urinary antigen testing and polymerase chain reaction (PCR) detection of bacterial and viral genes, have not only made documentation of etiology more accurate but will allow diagnosis of a greater proportion of cases. Accurate epidemiologic data regarding etiology of pneumonia are critical for empirical antibiotic prescription but guideline development groups suffer from lack of accurate current data. Interest in the use of biomarkers, such as procalcitonin, to distinguish between bacterial and viral infections is being driven by increasing concern about resistance and antibiotic-induced complications associated with inappropriate prescriptions. All of these factors coalesce on the need for a contemporary population-based estimate of CAP incidence based on a high proportion of cases with accurate etiologic diagnosis. In response to this need and the resultant CDC Funding Opportunity, we have developed a consortium of urban Chicago hospitals, in order to recruit 1000 adults and 300 children per year for two years. An accurate population-based estimate of incidence requires inclusion of an urban population with the variety of racial/ethnic and socioeconomic groups and with the variable access to healthcare characterizing patients admitted to these hospitals. Concern regarding the increase in frequency of community-acquired methicillin- resistant S. aureus (CA-MRSA) pneumonia also suggests that Chicago is an appropriate site for study, based on the high rate of CA-MRSA skin colonization. We will use an innovative geographic analysis based on zip code and public databases to determine the population-based incidence. Microbial etiology will be determined by extensive diagnostic testing, including routine urinary antigen detection, paired serology, and a battery of CDC-approved PCR assays of nasopharyngeal swabs. The role of influenza in bacterial pneumonia, especially pneumococcal and CA-MRSA, will be aggressively explored with PCR, culture, and paired serology. We will also validate a whole blood quantitative PCR of a pneumococcal gene to increase the diagnostic sensitivity and for potential risk-stratification of patients at the time of admission. The extensive diagnostic testing in this protocol also offers an excellent opportunity to validate the ability of procalcitonin, a clinically available biomarker, to distinguish between viral and bacterial pneumonia. PUBLIC HEALTH RELEVANCE: Community-acquired pneumonia, often complicating influenza or other viral infections, remains an important cause of death in the US. Patient risk factors, antibiotic resistance, and the bacteria and viruses that cause pneumonia have changed in recent years. This study will clearly define the incidence of pneumonia in an urban population and determine the microorganisms causing these pneumonias by addition of new molecular diagnostic tests. This information is critical to design appropriate future prevention and treatment plans.